Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001044438 | SCV001208236 | uncertain significance | Hypertrophic cardiomyopathy | 2023-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1588 of the MYH7 protein (p.Arg1588His). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 842087). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Color Diagnostics, |
RCV001525767 | SCV001735952 | uncertain significance | Cardiomyopathy | 2022-05-12 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 1588 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (Estevez et al. 2020, DOI: 10.1093/ehjci/ehaa946.0340). This variant has been identified in 2/251474 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002339223 | SCV002638642 | uncertain significance | Cardiovascular phenotype | 2022-10-17 | criteria provided, single submitter | clinical testing | The p.R1588H variant (also known as c.4763G>A), located in coding exon 32 of the MYH7 gene, results from a G to A substitution at nucleotide position 4763. The arginine at codon 1588 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV001525767 | SCV005430793 | uncertain significance | Cardiomyopathy | 2024-08-06 | criteria provided, single submitter | clinical testing |